AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells.

Khorraminejad-Shirazi M, Sani M, Talaei-Khozani T, Dorvash M, Mirzaei M, Faghihi MA, Monabati A, Attar A

Stem cell research & therapy3 Feb 2020Cited by 21 (Europe PMC)

PMID32014016PMCIDPMC6998366DOI10.1186/s13287-020-1565-6PepBankPUB-32014016

Summary

BackgroundMesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1).MethodsHuman adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups.ResultsMSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.ConclusionsSelective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs' self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

9 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Efficacy outcome
In human MSCs, AICAR increased proliferation compared with control medium.
In plain wordsIn cells, AICAR increased proliferation compared with control medium.
Peptide
AICAR (acadesine)
Outcome
IncreaseProliferation
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Cell proliferation and differentiation · Whole body
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401601
02LabIn vitro (cells)Efficacy outcome
In human MSCs, AICAR increased osteogenic differentiation compared with control medium.
In plain wordsIn cells, AICAR increased bone-forming differentiation compared with control medium.
Peptide
AICAR (acadesine)
Outcome
IncreaseOsteogenic differentiation
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Bone and joint · Musculoskeletal
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401602
03LabIn vitro (cells)Mechanism
In human MSCs, AICAR decreased β-galactosidase expression compared with control medium.
In plain wordsIn cells, AICAR reduced β-galactosidase expression compared with control medium.
Peptide
AICAR (acadesine)
Outcome
Decreaseβ-galactosidase expression
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Aging markers · Aging and longevity
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401605
04LabIn vitro (cells)Mechanism
In human MSCs, AICAR reduced dysfunctional lysosome accumulation compared with control medium.
In plain wordsIn cells, AICAR reduced dysfunctional lysosome accumulation compared with control medium.
Peptide
AICAR (acadesine)
Outcome
DecreaseDysfunctional lysosome accumulation
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Aging markers · Aging and longevity
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401606
05LabIn vitro (cells)Efficacy outcome
In human MSCs, AICAR produced morphological features characteristic of young MSCs.
In plain wordsIn cells, AICAR produced features characteristic of young cells compared with control medium.
Peptide
AICAR (acadesine)
Outcome
Not applicableYoung-cell morphology
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Aging markers · Aging and longevity
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401607
06LabIn vitro (cells)Mechanism
In aged human MSCs, AICAR did not significantly reduce total cellular ROS.
In plain wordsIn cells, AICAR did not significantly reduce reactive oxygen species compared with control medium.
Peptide
AICAR (acadesine)
Outcome
No significant changeTotal cellular ROS
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
normal medium control
Outcome group
Oxidative stress · Whole body
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401608
07LabIn vitro (cells)Safety outcome
In human MSCs, AICAR-treated cells showed the highest cellular apoptosis level.
In plain wordsIn cells, AICAR treatment produced the highest cell death level among the groups.
Peptide
AICAR (acadesine)
Outcome
IncreaseCellular apoptosis
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
other treatment groups
Outcome group
Cell viability and death · Whole body
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401609
08LabIn vitro (cells)Efficacy outcome
In human MSCs, combined AICAR and NAM augmented proliferation more than NAM alone.
In plain wordsIn cells, adding AICAR to NAM increased proliferation compared with NAM alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseProliferation with AICAR added to NAM
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
NAM alone
Outcome group
Cell proliferation and differentiation · Whole body
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401613
09LabIn vitro (cells)Efficacy outcome
In human MSCs, combined AICAR and NAM augmented osteogenic differentiation more than NAM alone.
In plain wordsIn cells, adding AICAR to NAM increased bone-forming differentiation compared with NAM alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseOsteogenic differentiation with AICAR added to NAM
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
NAM alone
Outcome group
Bone and joint · Musculoskeletal
Studied dose
1 mM · 5 weeksAs given in this study (human).
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
Show in the study text Report a problemFND-3201401614

Studies that did not test the peptide alone5

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

10LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Efficacy outcome
In human MSCs, combined AICAR and NAM augmented proliferation more than AICAR alone.
In plain wordsIn cells, combined AICAR and NAM increased proliferation more than AICAR alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseProliferation with combination
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
AICAR alone
Outcome group
Cell proliferation and differentiation · Whole body
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3201401603
11LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Efficacy outcome
In human MSCs, combined AICAR and NAM augmented osteogenic differentiation more than AICAR alone.
In plain wordsIn cells, combined AICAR and NAM increased bone-forming differentiation more than AICAR alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseOsteogenic differentiation with combination
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Comparator
AICAR alone
Outcome group
Bone and joint · Musculoskeletal
Source sentences
Summary
MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3201401604
12LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In human MSCs, effects of AICAR and NAM were associated with attenuated mTORC1 activity.
In plain wordsIn cells, AICAR and NAM effects accompanied lower mTORC1 activity.
Peptide
AICAR (acadesine)
Outcome
DecreasemTORC1 activity
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3201401610
13LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In human MSCs, effects of AICAR and NAM were associated with increased AMPK activity.
In plain wordsIn cells, AICAR and NAM effects accompanied increased AMPK activity.
Peptide
AICAR (acadesine)
Outcome
IncreaseAMPK activity
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3201401611
14LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In human MSCs, effects of AICAR and NAM were associated with increased autophagy.
In plain wordsIn cells, AICAR and NAM effects accompanied increased autophagy.
Peptide
AICAR (acadesine)
Outcome
IncreaseAutophagy
Study
humann: not reported in source
adipose-derived mesenchymal stromal cells
Outcome group
Receptor activity and mechanism · Whole body
Source sentences
Summary
The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3201401612

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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